Efficacy of cabazitaxel in patients with HER2-negative metastatic breast cancer
| ISRCTN | ISRCTN79877830 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN79877830 |
| EudraCT/CTIS number | 2012-000542-35 |
| Secondary identifying numbers | RDD490 |
- Submission date
- 06/02/2013
- Registration date
- 20/06/2013
- Last edited
- 17/03/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Dr Zafar Malik
Scientific
Scientific
The Clatterbridge Cancer Centre NHS Foundation Trust
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom
Ms Helen Scott
Public
Public
Cancer Research UK Liverpool Cancer Trials Unit
Block C, Waterhouse Building
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
| Phone | +44 (0)151 794 8209 |
|---|---|
| hscott@liv.ac.uk |
Study information
| Study design | Single-arm Phase II study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Phase II multicentre study assessing the efficacy of Cabazitaxel in Patients with HER2-negative metastatic breast cancer and having unresectable brain metastases (CiPHER) |
| Study acronym | CiPHER |
| Study objectives | Cabazitaxel is an effective cytotoxic agent that crosses the blood brain barrier and we hope to investigate this attribute in this Phase II study across several UK recruitment centres. Potentially this therapy could afford survival advantage. The primary aim of this study is to assess the feasibility of Cabazitaxel use in breast cancer with brain metastases by determining whether there is evidence for Cabazitaxel increasing 18 week survival from 67% to 81%. The study will require a maximum of 62 patients. The trial would be terminated for futility if 21 or fewer patients out of the first 31 survive to 18 weeks. Otherwise, the remaining 31 patients will be recruited (unless advised to the contrary by the DMC) and the null hypothesis will be rejected if there are more than 47 survivors at 18 weeks out of the 62 patients. |
| Ethics approval(s) | NRES Committee North West Liverpool Central, 22/05/2013, REC ref: 13/NW/0153 |
| Health condition(s) or problem(s) studied | Patients with HER2-negative metastatic breast cancer and having unresectable brain metastases. |
| Intervention | Patients on this study will receive cabazitaxel chemotherapy treatment and palliative radiotherapy will be deferred until evidence of disease progression. These patients will be monitored clinically and radiologically every three and six weeks respectively. Cabazitaxel 25 mg/m2 given on day 1 of each treatment cycle, intravenously, for one hour every 21 days. Diagnostic biopsy of primary tissue, urine samples (baseline and end of treatment) and blood samples (baseline, day 1 of each cycle and at end of treatment) will be collected, processed and stored for future research purposes. This will be with the aim of identifying serum and urinary biomarkers of predictive and prognostic significance. Baseline diagnostic tissues will be used for gene expression profiling and linked with serum and urinary biomarkers and proteomic profiles to identify markers of efficacy, resistance and toxicity. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Cabazitaxel |
| Primary outcome measure | Overall proportion surviving at 18 weeks from registration |
| Secondary outcome measures | 1. Progression-free survival (PFS) defined as the time from registration to the first of one of the following: development of disease progression or death from any cause 2. Overall response for extracranial visceral metastases (ORv) as defined in RECIST 1.0 , recorded from the start of treatment to 18 weeks 3. Overall response for CNS lesions (ORc) defined as a best response of at least PR, recorded from the start of treatment to 18 weeks 4. Acute toxicity (CTCAE v4) after each treatment cycle up to 18 weeks (for the purposes of safety, toxicity will be assessed up until 28 days after the last dose of study treatment) 5. Time to radiotherapy (measured from treatment start date until commencement of radiotherapy) 6. Time to neurological deterioration |
| Overall study start date | 01/03/2012 |
| Completion date | 25/07/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 62 |
| Total final enrolment | 19 |
| Key inclusion criteria | First or second line metastatic HER2 negative* breast cancer 1. Oligometastatic brain disease that is unsuitable for surgical resection and/or stereotactic radiosurgery 2. Age 18 years or over 3. ECOG performance status 0-2 4. Diagnosis of metastatic HER2-negative breast cancer 5. At least one measurable target lesion (RECIST 1.0) in the brain** (unsuitable for resection) identified by CT scan or MRI within 21 days of registration. 6. Females of child bearing potential who have a negative pregnancy test prior to study entry 7. Agree to use adequate contraception which they agree to continue for 12 months after the study treatment 8. Ability and capacity to comply with study and follow-up procedure 9. Able to provide written informed consent *Patients with ER+ve or ER-ve disease are eligible for the study ** Patients with meningeal disease are eligible provided they fit the other criteria. Extracranial disease is not a requirement of this study. |
| Key exclusion criteria | 1. Received prior radiotherapy/radiosurgery to the brain (radiotherapy may be offered on disease progression) 2. Received >2 lines of chemotherapy for metastatic recurrent disease (adjuvant treatment is permitted) prior to registration 3. Received any chemotherapy after the diagnosis of brain metastases 4. Previous hormone therapy if it will not be discontinued before Cabazitaxel treatment 5. Patients who have received an increasing dose of steroids to control CNS symptoms within 14 days of registration (steroid use is permitted only when patient is stable at a specific dose at the time of screening) 6. Visceral metastases with no recorded brain metastases 7. Pregnancy or lactation 8. Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 28 days prior to registration 9. Patients with a history of other previous malignancy except treated CIN or non melanomatous skin cancer 10. Grade ≥2 peripheral motor and/or sensory neuropathy 11. Grade ≥2 mucositis oral 12. History of severe hypersensitivity reaction (≥grade 3) to taxanes 13. History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80-containing drugs 14. Other concurrent serious illness or medical conditions which make it undesirable for the patient to enter the trial (including uncontrolled diabetes mellitus) 15. Inadequate organ and bone marrow function as evidenced by: 15.1. Haemoglobin < 9.0 g/dL 15.2. Absolute neutrophil count < 1.5 x 109/L 15.3. Platelet count <100 x 109/L 15.4. AST/SGOT and/or ALT/SGPT >2.5 x ULN 15.5. total bilirubin >1.0 x ULN 15.6. Serum creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded 16. Active infection requiring systemic antibiotic or anti fungal medication. 17. Participation in another clinical trial with any investigational drug within 30 days prior to registration 18. Administration of potent inhibitors and inducers of P450 3A4/5 enzymes within 7 days of registration, or planned concurrent administration whilst on study. This excludes steroid treatment which is standard care treatment for patients with brain metastases 19. Concomitant vaccination with live attenuated vaccines |
| Date of first enrolment | 01/03/2012 |
| Date of final enrolment | 05/12/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
The Clatterbridge Cancer Centre NHS Foundation Trust
Wirral
CH63 4JY
United Kingdom
CH63 4JY
United Kingdom
Sponsor information
The Clatterbridge Cancer Centre NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Clatterbridge Road
Bebington
Wirral
CH63 4JY
England
United Kingdom
"ROR" |
https://ror.org/05gcq4j10 |
|---|
Funders
Funder type
Industry
Sanofi: CABAZ_L_5958
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- sanofi-aventis, Sanofi US, Sanofi-Aventis U.S. LLC, Sanofi U.S.
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/03/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 28/05/2020 | No | No | ||
| Plain English results | 17/03/2021 | No | Yes | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
17/03/2021: CRUK link added to plain English results.
28/05/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
15/04/2019: The following changes have been made:
1. The scientific contact's details have been updated.
2. A public contact has been added.
3. The overall trial end date has been changed from 05/12/2017 to 25/07/2018.
4. An intention to publish date has been added.
14/05/2018: The overall trial end date was changed from 01/03/2016 to 05/12/2017.
